Distant organ metastasis patterns and prognosis of cervical adenocarcinoma: a population-based retrospective study.

Background: Adenocarcinoma is a common histological subtype of cervical cancer, accounting for 10-15% of all cases. The prognosis of cervical adenocarcinoma with distant organ metastases remains unclear. Therefore, our study aimed to investigate the patterns and prognosis of distant organ metastasis in cervical adenocarcinoma. Methods: We obtained data from the Surveillance, Epidemiology, and End Results (SEER) database spanning from 2010 to 2019. Cox regression, Kaplan-Meier, and log-rank analyses were conducted. Results: We observed that adenocarcinoma (AC) of the cervix primarily metastasizes to single organs, with a rate of 73.3%. The lungs are the most common organs of metastasis, followed by the liver and bones. Patients with bone metastases have a median survival period of 12 months, which is slightly longer compared to metastasis in other organs. Distant organ metastasis, age, positive lymph nodes, higher AJCC stages, larger tumor diameter, and higher cell grades are related to poor prognosis (p < 0.001). Furthermore, we have observed that surgical intervention, radiotherapy, and chemotherapy can potentially provide benefits for patients with distant organ metastases. Conclusion: Metastasis is an independent prognostic factor for cervical adenocarcinoma patients. Surgery, radiotherapy, and chemotherapy can provide an overall survival advantage for patients with distant organ metastases.

P16/Ki67 Dual Staining in Glandular Cell Abnormalities of the Uterine Cervix.

Very limited information exists about the role of p16/Ki67 dual staining on glandular cells in detecting glandular precancerous lesions and cervical adenocarcinoma. In this study, we investigated the diagnostic accuracy of p16/Ki67 dual staining for the detection of glandular and squamous lesions on the uterine cervix and for cancer of the upper reproductive tract. We performed a retrospective analysis of prospectively collected data on 96 patients with glandular cell abnormalities. We analyzed the diagnostic accuracy of p16/Ki67 dual staining for atypical glandular cells, not otherwise specified (AGC-NOS); atypical glandular cells, favor neoplastic (AGC-FN); adenocarcinoma in situ (AIS); and A-CA (cervical adenocarcinoma). A separate analysis for the detection of squamous precancerous lesions and squamous-cell carcinoma (CIN3+) and for cancer of the upper reproductive tract (EC/OC) was performed. Among patients who had normal histology or a low-grade lesion on final analysis, only 8.5% had positive dual staining. On the other hand, 85.7% of patients with AIS+ on final histology had positive dual staining. The respective specificities of p16/Ki67 dual staining on AGC-NOS for the detection of AIS+ (adenocarcinoma in situ or cervical adenocarcinoma), CIN3+ and EC/OC were 91.5%, 88.7% and 86.4%. High specificity values of p16/Ki67 dual staining on cervical smears labelled as AGC-NOS for the detection of CIN3+ and AIS+ suggest that this method might be a useful addition in cervical cancer screening.

Hormone Replacement Therapy in Post-Menopause Hormone-Dependent Gynecological Cancer Patients: A Narrative Review.

BACKGROUND: Advances in the treatment of gynecological cancer have led to improvements in survival but also an increase in menopausal symptoms, especially in young women with premature iatrogenic menopause. METHODS: A narrative review was performed to clarify the possibility of prescribing hormone replacement therapy (HRT) after hormone-dependent gynecological cancers (ovarian cancer [OC], cervical adenocarcinoma [AC], and endometrial cancer [EC]). RESULTS: HRT can be prescribed to patients with early-stage, grade I-II OC who experience bothersome menopausal symptoms non-responsive to alternative non-hormone therapy after optimal surgery. Caution should be exercised in administering HRT after serous borderline tumors and endometrioid OC, and HRT is not recommended in low-grade serous OC. HRT is not contraindicated in AC survivors. After surgery for EC, HRT can be prescribed in women with early-stage low-grade EC. There is not enough data to give indications to patients with advanced EC. CONCLUSIONS: HRT can be discussed with patients, evaluating the risks and benefits of hormone-dependent gynecological cancer. Counseling should be performed by gynecologic oncologists experienced in the management of these patients.

Stratified Prognostic Comparison Between Stage IIB-IVA Cervical Adenocarcinoma and Squamous Cell Carcinoma: A SEER Database-Based Study.

Objective: In current most observational studies, the prognosis of cervical adenocarcinoma is worse than that of cervical squamous cell carcinoma. However, most of the current studies are holistic and lack more detailed staging and grouping analysis of the prognosis of the two types of cervical tumors. Patients and Methods: Inclusion from the SEER database of stage IIB-IVA cervical squamous cell carcinoma and cervical adenocarcinoma patients who did not undergo surgery from 2000 to 2019, underwent radiotherapy/chemotherapy/radiotherapy and chemotherapy/no treatment, and then propensity score matching (PSM) was performed to eliminate confounding factors between cervical squamous cell carcinoma and cervical adenocarcinoma patients with the same stage and treatment method. After matching the original data and propensity score, logarithmic rank test and chi square test were used to evaluate the survival benefits of different stages and treatment methods for patients using Kaplan Meier curve. The prognosis of two types of cervical tumors under the same treatment method was compared, and factors that may cause poor prognosis were analyzed, excluding confounding factors. Results: A total of 10,057 patients were included in this study, and survival analysis showed a significant correlation between the treatment method used and patient prognosis (P<0.05). However, for patients who received radiotherapy or no special treatment, OS and CSS were only related to tumor stage and not to tumor type. In patients undergoing radiotherapy and chemotherapy, the OS and CSS of stage IIIA and IVA patients are not related to tumor pathological characteristics, while the OS of stage IIB patients is not related to tumor properties after PSM. Conclusion: In patients undergoing radiotherapy and chemotherapy, the OS and CSS of stage IIIA and IVA patients were not related to histological type, while the OS of stage IIB patients was not related to histological type after PSM.

Gene Expression Analysis for Uterine Cervix and Corpus Cancer Characterization.

The analysis of gene expression quantification data is a powerful and widely used approach in cancer research. This work provides new insights into the transcriptomic changes that occur in healthy uterine tissue compared to those in cancerous tissues and explores the differences associated with uterine cancer localizations and histological subtypes. To achieve this, RNA-Seq data from the TCGA database were preprocessed and analyzed using the KnowSeq package. Firstly, a kNN model was applied to classify uterine cervix cancer, uterine corpus cancer, and healthy uterine samples. Through variable selection, a three-gene signature was identified (VWCE, CLDN15, ADCYAP1R1), achieving consistent 100% test accuracy across 20 repetitions of a 5-fold cross-validation. A supplementary similar analysis using miRNA-Seq data from the same samples identified an optimal two-gene miRNA-coding signature potentially regulating the three-gene signature previously mentioned, which attained optimal classification performance with an 82% F1-macro score. Subsequently, a kNN model was implemented for the classification of cervical cancer samples into their two main histological subtypes (adenocarcinoma and squamous cell carcinoma). A uni-gene signature (ICA1L) was identified, achieving 100% test accuracy through 20 repetitions of a 5-fold cross-validation and externally validated through the CGCI program. Finally, an examination of six cervical adenosquamous carcinoma (mixed) samples revealed a pattern where the gene expression value in the mixed class aligned closer to the histological subtype with lower expression, prompting a reconsideration of the diagnosis for these mixed samples. In summary, this study provides valuable insights into the molecular mechanisms of uterine cervix and corpus cancers. The newly identified gene signatures demonstrate robust predictive capabilities, guiding future research in cancer diagnosis and treatment methodologies.

Multiparametric MRI-based radiomics nomogram for identifying cervix-corpus junction cervical adenocarcinoma from endometrioid adenocarcinoma.

OBJECTIVE: To developed a magnetic resonance imaging (MRI) radiomics nomogram to identify adenocarcinoma at the cervix-corpus junction originating from the endometrium or cervix in order to better guide clinical treatment. METHODS: Between February 2011 and September 2021, the clinicopathological data and MRI in 143 patients with histopathologically confirmed cervical adenocarcinoma (CAC, n = 86) and endometrioid adenocarcinoma (EAC, n = 57) were retrospectively analyzed at the cervix-corpus junction. Radiomics features were extracted from fat-suppressed T2-weighted imaging (FS-T2WI), diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) maps, and delayed phase contrast-enhanced T1-weighted imaging (CE-T1WI) sequences. A radiomics nomogram was developed integrating radscore with independent clinical risk factors. The area under the curve (AUC) was used to evaluate the diagnostic efficacy of the radscore, nomogram and two different experienced radiologists in differentiating CAC from EAC at the cervix-corpus junction, and Delong test was applied to compare the differences of their diagnostic performance. RESULTS: In the training cohort, the AUC was 0.93 for radscore; 0.97 for radiomics nomograms; 0.85 and 0.86 for radiologists 1 and 2, respectively. Delong test showed that the differential efficacy of nomogram was significant better than those of radiologists in the training cohort (both P < 0.05). CONCLUSIONS: The nomogram based on radscore and clinical risk factors could better differentiate CAC from EAC at the cervix-corpus junction than radiologists, and preoperatively and non-invasively identify the origin of adenocarcinoma at the cervix-corpus junction, which facilitates clinicians to make individualized treatment decision.

Diagnostic challenges and individualized treatment of cervical adenocarcinoma metastases to the breast: A case report.

BACKGROUND: Cervical cancer is a rare primary tumor resulting in metastases to the breast with few cases reported in literature. Breast metastases are associated with poor prognosis. The following case highlights the diagnostic challenges associated with metastatic cervical cancer to the breast along with individualized treatment. CASE SUMMARY: A 44-year-old G7P5025 with no significant past medical or surgical history presented with heavy vaginal to an outside emergency department where an exam and a pelvic magnetic resonance imaging showed a 4.5 cm heterogenous lobulated cervical mass involving upper two thirds of vagina, parametria and lymph node metastases. Cervical biopsies confirmed high grade adenocarcinoma with mucinous features. A positron emission tomography/computed tomography (PET/CT) did not show evidence of metastatic disease. She received concurrent cisplatin with external beam radiation therapy. Follow up PET/CT scan three months later showed no suspicious fluorodeoxyglucose uptake in the cervix and no evidence of metastatic disease. Patient was lost to follow up for six months. She was re-imaged on re-presentation and found to have widely metastatic disease including breast disease. Breast biopsy confirmed programmed death-ligand 1 positive metastatic cervical cancer. The patient received six cycles of carboplatin and paclitaxel with pembrolizumab. Restaging imaging demonstrated response. Patient continued on pembrolizumab with disease control. CONCLUSION: Metastatic cervical cancer to the breast is uncommon with nonspecific clinical findings that can make diagnosis challenging. Clinical history and immunohistochemical evaluation of breast lesion, and comparison to primary tumor can support diagnosis of metastatic cervical cancer to the breast. Overall, the prognosis is poor, but immunotherapy can be considered in select patients and may result in good disease response.

Predicting the recurrence of usual-type cervical adenocarcinoma using a nomogram based on clinical and pathological factors: a retrospective observational study.

Background: Usual-type cervical adenocarcinoma is the most frequent type of adenocarcinoma, and its prevalence is increasing worldwide. Tumor recurrence is the leading cause of mortality; therefore, recognizing the risk factors for cervical cancer recurrence and providing effective therapy for recurrent cervical cancer are critical steps in increasing patient survival rates. This study aimed to retrospectively analyze the clinicopathological data of patients with usual-type cervical adenocarcinoma by combining the diagnosis and treatment records after the initial treatment and recurrence. Methods: We retrospectively analyzed patients diagnosed with usual-type cervical adenocarcinoma who underwent radical hysterectomy and pelvic lymph node dissection at Shengjing Hospital of China Medical University between June 2013 and June 2022. We constructed a nomogram-based postoperative recurrence prediction model, internally evaluated its efficacy, and performed internal validation. Results: This study included 395 participants, including 87 individuals with recurrence. At a 7:3 ratio, the 395 patients were divided into two groups: a training set (n = 276) and a validation set (n = 119). The training set was subjected to univariate analysis, and the risk variables for recurrence included smoking, ovarian metastasis, International Federation of Gynaecology and Obstetrics (FIGO) staging, lymphovascular space invasion, perineural invasion, depth of muscular invasion, tumor size, lymph node metastasis, and postoperative HPV infection months. The aforementioned components were analyzed using logistic regression analysis, and the results showed that the postoperative HPV infection month, tumor size, perineural invasion, and FIGO stage were independent risk factors for postoperative recurrence (p<0.05). The aforementioned model was represented as a nomogram. The training and validation set consistency indices, calculated using the bootstrap method of internal validation, were 0.88 and 0.86, respectively. The model constructed in this study predicted the postoperative recurrence of usual-type cervical cancer, as indicated by the receiver operating characteristic curve. The model demonstrated good performance, as evidenced by the area under the curve, sensitivity, and specificity values of 0.90, 0.859, and 0.844, respectively. Conclusion: Based on the FIGO staging, peripheral nerve invasion, tumor size, and months of postoperative HPV infection, the predictive model and nomogram for postoperative recurrence of usual-type cervical adenocarcinoma are precise and effective. More extensive stratified evaluations of the risk of cervical adenocarcinoma recurrence are still required, as is a thorough assessment of postoperative recurrence in the future.

Our experience diagnosing 225 patients with cervical glandular lesions: current technologies, lessons learned, and areas for improvement.

OBJECTIVE: To explore the relative sensitivity of different methods for detecting cervical glandular lesions. METHODS: A total of 225 patients with cervical glandular lesions diagnosed from January 2018 to February 2023 were retrieved from the pathology database of Guangdong Maternal and Child Health Hospital, and their clinicopathological features were reviewed. RESULTS: Four human papillomavirus (HPV) genotypes: HPV18, 16, 45, and 52, dominated all glandular lesions, and accounting for 74.10% of HPV-positive tumors. Furthermore, 36.89% of abnormal squamous cells were diagnosed as abnormal based on cytological examinations leading to the detection of cervical glandular lesions; only 16.89% were diagnosed based on the initial detection of abnormal glandular cytology. The most common abnormal cervical screening result was ASC-US on cytology (14.22%), followed by HSIL (11.56%). Only few number of patients were diagnosed with or suspected of having cervical adenopathy via a Pap test (18.22%). Nearly one-third of cervical glandular lesions cases were not detected on the Pap test; but were diagnosed upon cervical biopsy or based on the histological examination of ECC, LEEP, or CKC specimens. The LEEP or CKC biopsy specimens had negative margins in 49 cases (40.83%), while the margins were positive in the other 71 cases (59.17%). Five cases (10.20%) with negative margins still had residual lesions following total hysterectomy, and 19 (26.76%) with positive margins had no residual lesions after total hysterectomy. CONCLUSION: The ability to detect cervical glandular lesions varies for routine HPV genotyping, Pap test, or biopsy/ECC, with different sensitivities and advantages and disadvantages for each method.

Zimberelimab combined with systemic therapy extended tumor control in post-radiotherapy cervical cancer with brain metastases: A case report.

Out of the total cases of cervical cancer, brain metastases (BMs) are relatively rare, with an estimated incidence rate of 0.63% (range: 0.1%-2.2%). Additionally, BMs prognosis remains poor, and the average patient survival time following a BM diagnosis is 3 to 5 months. Few studies have addressed the effect of programmed cell death-1 inhibitors against BMs in cervical cancer, although they are an established option for recurrent/metastatic disease. Hence, we report a case involving a 54-year-old post-surgery patient with cervical cancer with a body mass index of 19.5 kg/m2 and Eastern Collaborative Oncology Group (ECOG) performance status of 3; the disease recurred with BMs 1 year later. Intensity-modulated radiation therapy concurrent with temozolomide and bevacizumab was initiated, following which zimberelimab immunotherapy combined with anlotinib was administered to extend tumor control. The patient had a progression-free survival duration of 10 months, the tumor response was assessed as a partial response based on the evaluation criteria for solid tumors (RECIST1.1), and the ECOG status improved to 1 after therapy. These findings suggest that immunotherapy-based combination therapy following radiotherapy may be a good choice for patients with cervical cancer and BMs.

Characteristics of HPV integration in cervical adenocarcinoma and squamous carcinoma.

PURPOSE: HPV integration usually occurs in HPV-related cancer, and is the main cause of cancer. But the carcinogenic mechanism of HPV integration is unclear. The study aims to provide a theoretical basis for understanding the pathogenesis of cervical adenocarcinoma (AC) and cervical squamous carcinoma (SCC). METHODS: We used HPV capture sequencing to obtain HPV integration sites in AC and SCC, and analyzed cytobands, distribution of genetic and genomic elements, identified integration hotspot genes, clinicopathological parameters, breakpoints of HPV16 and performed pathway analysis. Then we conducted immunohistochemical (IHC) assay to preliminarily verify the expression of most frequently integrated genes in AC, STARD3 and ERBB2. RESULTS: The results revealed that the most frequently observed integrated cytoband was 17q12 in AC and 21p11.2 in SCC, respectively. The breakpoints in both AC and SCC were more tended to occur within gene regions, compared to intergenetic regions. Compared to SCC samples, AC samples had a higher prevalence of genomic elements. In AC, HPV integration has no significantly difference with clinicopathological parameters, but in SCC integration correlated with differentiation (P < 0.05). Breakpoints of HPV in SCC located in LCR more frequently compared to AC, which destroyed the activation of promoter p97. Hotspot genes of HPV integration were STARD3 and ERBB2 in AC, and RNA45S rDNA and MIR3648-1 in SCC, respectively. Meanwhile, we preliminarily proved that the expression of STARD3 and ERBB2, the most frequently integrated genes, would increase after integration. CONCLUSION: These results suggested that HPV may utilize the powerful hosts' promoters to express viral oncogenes and overexpression of viral oncogenes plays a significant role in the carcinogenesis of SCC. In AC, HPV integration may affect hosts' oncogenes, and the dysregulation of oncogenes may primarily contribute to progression of AC.

Identifying tumor markers-stratified subtypes (CA-125/CA19-9/carcinoembryonic antigen) in cervical adenocarcinoma.

OBJECTIVE: There is a lack of research evaluating the effect of tumor markers for prognosis in cervical adenocarcinoma. We aimed to develop and validate a preoperative tumor-marker-based model including clinicopathological factors to clarify the prognostic value of endocervical adenocarcinoma. METHODS: A total of 572 patients with cervical adenocarcinoma who were staged at the International Federation of Gynecology and Obstetrics (FIGO) IA-IIA were reviewed retrospectively. Preoperative serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA)-125 and CA19-9 levels were measured. The survival and recurrence patterns were analyzed according to the tumor-marker-related stratification. The predictive values of biomarkers and clinical variables were assessed with Cox regression and competing risk models. RESULTS: Patients with elevated preoperative tumor markers had evidently poor overall survival and recurrence-free survival. The triple-elevated tumor marker (TETM) subgroup had the worst overall survival and progression-free survival than the triple-negative tumor marker (TNTM) subgroup and the single-elevated tumor marker (SETM) subgroup. The most important predictors for overall survival were elevated tumor markers, FIGO-stage, tumor differentiation, lymphovascular space invasion (LVSI) and lymph nodes metastasis. The most important predictors for recurrence-free survival were elevated tumor markers, FIGO-stage, tumor differentiation, LVSI and deep stromal invasion. Stratified analysis showed that elevated CA-125 and CA19-9 were significantly associated with postoperative distant metastasis. A decision curve analysis confirmed that a combination of tumor markers as predictors significantly outperformed the other common predictors used (FIGO-stage, intermediate and high-risk factors, tumor differentiation, lymph nodes). CONCLUSIONS: Elevated preoperative serum CEA, CA-125, and CA19-9 levels exhibited poor overall survival and recurrence-free survival in cervical adenocarcinoma patients. Combined preoperative serum CA-125 and CA19-9 independently predicted distant metastasis in patients with endocervical adenocarcinoma.

Prevalence and genotype distribution of human papillomavirus in cervical adenocarcinoma (usual type and variants): A systematic review and meta-analysis.

Cervical glandular neoplasms represent a heterogeneous group of tumors for which a comprehensive overview of the involvement of high-risk human papillomaviruses (HPV) in pathogenesis is still lacking. We first searched MEDLINE (PubMed), Embase, and Scopus databases (until October 2022), and systematically reviewed available literature. We then quantitatively estimated both pooled and genotype-specific prevalence of HPV DNA as well as the influence of various factors (e.g., geographical region, histological subtype, tissue/sample type) on computed effect size by means of random effects meta-analysis. In total, 379 studies comprising 17 129 cases of cervical adenocarcinoma were identified. The pooled HPV prevalence was 78.4% (95% confidence interval [95% CI]: 76.2-80.3) with a significant between-study heterogeneity (I2 = 79.4%, Q test p < 0.0001). Subgroup analyses indicated that the effect size differed substantially by geographical region (from 72.5% [95% CI: 68.7-76.1] in Asia to 86.8% [95% CI: 82.2-90.3] in Oceania) (p < 0.0001) and histological subtype of cancer (from 9.8% [95% CI: 5.5-17] in gastric-type to 85% [95% CI: 79.6-89.2] in usual-type cervical adenocarcinoma) (p < 0.0001). HPV16 and HPV18 were by far the most frequently detected viral strains with specific prevalence of 49.8% (95% CI: 46.9-52.6) and 45.3% (95% CI: 42.8-47.8), respectively. When stratified by continent or histologic variant, these genotype-specific results varied in a relatively limited manner. Altogether, these findings support that all histological subtypes of cervical adenocarcinoma are etiologically linked to high-risk HPV but to varying degrees. Therefore, a dual-criteria classification taking into account accurately both morphological and virological aspects could be an interesting evolution of the current binary World Health Organization classification, better reflecting the pathogenic diversity of the disease.

Kynureninase knockdown inhibits cisplatin resistance in vivo and in vitro and impacts the prognosis of cervical adenocarcinoma.

BACKGROUND: Chemotherapy resistance is a leading cause of treatment failure in cases of cervical adenocarcinoma (ADC), and no effective treatment approach has yet been found. We previously identified the differentially expressed kynureninase (KYNU) mRNA in cervical adenocarcinoma cells (HeLa) and cervical adenocarcinoma cisplatin resistance cells (HeLa/DDP) using gene chips. However, the role and potential mechanism of KYNU in the cisplatin resistance of cervical adenocarcinoma remain unclear. METHODS: We verified the expression of KYNU in the cells and tissues of ADC patients and analyzed its correlation with patient prognosis. A stable HeLa/DDP cell line with KYNU mRNA knockdown was constructed. We then used a CCK8 assay to detect cell survival, a transwell assay to evaluate cell migration and proliferation and flow cytometry to measure apoptosis. The effect of KYNU silence on cisplatin sensitivity was evaluated in an orthotopic model of metastatic ADC. Immunohistochemistry was performed to determine the changes in relevant drug resistance-associated protein expression, aiming to explore the underlying mechanism of KYNU-mediated drug resistance. RESULTS: KYNU is overexpressed in HeLa/DDP cells and tissues and is associated with the poor prognoses of patients with ADC. After KYNU mRNA knockdown, the invasion, migration, and proliferation of HeLa/DDP cells in the cisplatin environment significantly reduced, while the apoptosis rate of HeLa/DDP cells significantly increased. Meanwhile, KYNU knockdown improved the DDP sensitivity of ADC in vivo. Furthermore, silencing KYNU decreased the expressions of CD34 and the drug-resistance related proteins P-gp, MRP1, and GST-π and increased the level of the proapoptotic regulatory protein Bax. CONCLUSION: KYNU deficiency enhanced DDP sensitivity by suppressing cell proliferation, migration, and invasion and promoting apoptosis in DDP-resistant ADC cells in vitro. Furthermore, KYNU knockdown improved the drug sensitivity of ADC in vivo. The results showed that KYNU is involved in the chemotherapy resistance of cervical adenocarcinoma.

Enhancing prognostic accuracy: a SEER-based analysis for overall and cancer-specific survival prediction in cervical adenocarcinoma patients.

BACKGROUND: Cervical adenocarcinoma (CA) is the second most prevalent histological subtype of cervical cancer, following cervical squamous cell carcinoma (CSCC). As stated in the guidelines provided by the National Comprehensive Cancer Network, they are staged and treated similarly. However, compared with CSCC patients, CA patients are more prone to lymph node metastasis and recurrence with a poorer prognosis. The objective of this research was to discover prognostic indicators and develop nomograms that can be utilized to anticipate the overall survival (OS) and cancer-specific survival (CSS) of patients diagnosed with CA. METHODS: Using the Surveillance, Epidemiology, and End Result (SEER) database, individuals with CA who received their diagnosis between 2004 and 2015 were identified. A total cohort (n = 4485) was randomly classified into two separate groups in a 3:2 ratio, to form a training cohort (n = 2679) and a testing cohort (n = 1806). Overall survival (OS) was the primary outcome measure and cancer-specific survival (CSS) was the secondary outcome measure. Univariate and multivariate Cox analyses were employed to select significant independent factors and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis was utilized to develop predictive nomogram models. The predictive accuracy and discriminatory ability of the nomogram were assessed by employing metrics such as the calibration curve, receiver operating characteristic (ROC) curve, and the concordance index (C-index). RESULTS: Age, Tumor Node Metastasis stages (T, N, and M), SEER stage, grade, and tumor size were assessed as common independent predictors of both OS and CSS. The C-index value of the nomograms for predicting OS was 0.832 (95% CI 0.817-0.847) in the training cohort and 0.823 (95% CI 0.805-0.841) in the testing cohort. CONCLUSION: We developed and verified nomogram models for predicting 1-, 3- and 5-year OS and CSS among patients with cervical adenocarcinoma. These models exhibited excellent performance in prognostic prediction, providing support and assisting clinicians in assessing survival prognosis and devising personalized treatments for CA patients.

Case Report: Pelvic mass and massive ascites as the first symptom in cervical adenocarcinoma: report of two cases and literature review.

Cervical adenocarcinoma accounts for 10%-25% of total cases of cervical carcinoma. But in recent years, the incidence of adenocarcinoma has risen both proportionally and absolutely. Clinically, most cervical adenocarcinoma show no symptom or present with abnormal uterine bleeding or vaginal discharge, similar to squamous cell carcinoma. What different about it is that cervical cytological testing demonstrates a high false-negative rate of cervical adenocarcinoma, potentially leading to the failure in detecting in early stage. This report presents two cases both with pelvic masses, and massive ascites served as the initial symptom, which is similar to the clinical symptom of ovarian cancer, but ultimately diagnosed with cervical adenocarcinoma through surgical specimens. There are few literature reports on this situation. Hence, a literature review also has been performed to improve the recognition for cervical adenocarcinoma presenting with pelvic masses and massive ascites, and to avoid misdiagnosis.

Anticancer effect of novel luteolin capped gold nanoparticles selectively cytotoxic towards human cervical adenocarcinoma HeLa cells: An in vitro approach.

BACKGROUND: Although luteolin has been confirmed as potent anticancer agent, its potential application as therapeutic is limited by its water solubility. To overcome this shortcoming nanoparticle technology approach was applied. Owing to their proven low toxicity and the possibility to be easily functionalized gold nanoparticles (AuNP) were the nanosystem of choice used in this study. Novel luteolin capped gold nanoparticles (AuNPL) were synthesized and their anticancer effect towards human cervical adenocarcinoma HeLa cells was investigated in vitro. METHODS: AuNPL were synthesized by reducing chloroauric acid by trisodium citrate with subsequent addition of luteoline during synthesis and their physicochemical characterization was done. AuNPL cytotoxicity against HeLa, human malignant melanoma A375, and normal human keratinocytes HaCaT cells was tested by MTT cell survival assay, and their IC50 values were determined. The capability of AuNPL to induce cell cycle arrest and apoptosis in HeLa cells were demonstrated by flow cytometry. The antioxidant activity of AuNPL was assessed by DPPH· and ABTS·+ scavenging assays. Cytoprotective properties of AuNPL towards HaCaT cells were examined by measuring the physiological and H2O2 induced intracellular reactive oxygen species (ROS) levels using flow cytometry. Also, genotoxicity of AuNPL in HaCaT cells was investigated by the single cell alkaline comet assay. RESULTS: Spherical AuNPL, stable in aqueous solution up to six months at 4 °C were obtained in the synthesis. The selectivity in the cytotoxic action of AuNPL on HeLa and A375 cancer cells compared with their cytotoxicity on normal keratinocytes HaCaT was observed. AuNPL exerted their cytotoxic activity against HeLa cells through accumulation of the cells in the subG1 phase of the cell cycle, inducing the apoptotic cell death mediated by the activation of caspase-3 - 8, and - 9. AuNPL antioxidative potential was confirmed by DPPH· and ABTS·+ scavenging assays. IC50 concentration of AuNPL exerted cytoprotective effect against HaCaT cells by the significant reduction of the physiological intracellular ROS level. Additionally, AuNPL were shown as more cytoprotective towards HaCaT cells then luteolin due to the more successful elimination of H2O2 induced intracellular ROS. Moreover, nontoxic concentrations of AuNPL did not cause considerable DNA damage of HaCaT cells, indicating low genotoxicity of the nanoparticles. CONCLUSION: Synthesized AuNPL showed selective cytotoxic activity against HeLa cells, while being nontoxic and cytoprotective against HaCaT cells. The observed findings encourage further investigation of AuNPL as a promising novel anticancer agent.

Isolated tubal metastasis from an incidental HPV-associated endocervical adenocarcinoma presented as an adnexal mass: A case report.

Tubal metastasis from endocervical adenocarcinoma is uncommon and is discovered as an incidental finding on routine sampling of fallopian tubes. In this paper, we present the case of an 81-year-old woman who presented with an adnexal mass during investigations of postmenopausal bleeding. Hysterectomy and bilateral salpingo-oophorectomy with excision of the left adnexal mass were performed, which led to the diagnosis of an incidental HPV-associated endocervical adenocarcinoma with secondary, macroscopic tubal involvement. The patient received adjuvant pelvic radiotherapy and remained well after three months of follow-up, with no evidence of recurrence. Only a few cases of endocervical adenocarcinoma with tubal metastasis have been reported in the literature, which are commonly associated with ovarian, uterine corpus, and/or parametrial tissue involvement. To date, there are only two reported cases of isolated tubal metastasis, and in both cases, tubal involvement was discovered microscopically. Data on the impact of secondary tubal involvement on patient outcomes are limited.

Development and validation of nomograms to recurrence and survival in patients with early-stage cervical adenocarcinoma.

PURPOSE: Cervical adenocarcinoma is one of the most common types of cervical cancer and its incidence is increasing. The biological behavior and treatment outcomes of cervical adenocarcinoma (CA) differ from those of squamous cell carcinoma (SCC). We sought to develop a model to predict recurrence and cancer-specific survival (CSS) deaths in CA patients. METHODS: 131 patients were included in model development and internal validation, and patients from the SEER database (N = 1679) were used for external validation. Multivariable Cox proportional hazards regression analysis was used to select predictors of relapse-free survival (RFS) and CSS and to construct the model, which was presented as two nomograms. Internal validation of the nomograms was performed using the bootstrap resampling method. RESULTS: Age, FIGO (International Federation of Gynecology and Obstetrics) stage, size of the tumor, lymph metastasis and depth of invasion were identified as independent prognostic factors for RFS, while age, FIGO stage, size of the tumor and number of positive LNs were identified as independent prognostic factors for CSS. The nomogram of the recurrence model predicted 2- and 5-year RFS, with optimism adjusted c-statistic of 75.41% and 74.49%. Another nomogram predicted the 2- and 5-year CSS with an optimism-adjusted c-statistic of 83.22% and 83.31% after internal validation; and 68.6% and 71.33% after external validation. CONCLUSIONS: We developed and validated two effective nomograms based on static nomograms or online calculators that can help clinicians quantify the risk of relapse and death for patients with early-stage CA.